High-Risk Pregnancy in Lupus Patients

Interviews with Experts

Dr. Paget: It is a pleasure today to introduce Dr. Terri Edersheim, Clinical Associate Professor of Obstetrics and Gynecology at the Weill Medical College of Cornell University. She is a superb obstetrician and gynecologist and has a particular interest in high-risk pregnancies and, I think, specifically in the area of lupus. Dr. Edersheim, pregnancy is an interesting state. Why can it be so affected by diseases such as the ones we take care of here?

Dr. Edersheim: The diseases that we take care of here are often manifested in blood vessels, and pregnancy should be thought of as an experiment in blood vessels -- that is what placentas are. Any condition that affects blood vessels will affect the pregnancy and vice versa - the pregnancy will affect the patient with the underlying vessel disease.

Dr. Paget: I think that is a wonderful concept. At least one hat that you wear is a high- risk pregnancy gynecologist and obstetrician. What does that mean, and who should be coming to see you?

Dr. Edersheim: The Board of Maternal and Fetal Medicine was started to take care of patients who have medical diseases in pregnancy and who have obstetrical issues in pregnancy. So, primarily, we take care of things like lupus, diabetes, hypertension, and renal diseases in pregnancy, as well as multiples in pregnancies -- such as triplets and twins -- or people with incompetent cervix. That is who should be coming to see us. But also, people who just have advanced maternal age. Because of in-vitro fertilization and assisted reproduction, we are seeing many women having babies after the age of 40. That is another group who come to see us.

Dr. Paget: Some of those disorders that you just mentioned support the concept that you mentioned in that they involve vascular-type problems. Let us move to systemic lupus erythematosus, which occurs predominately in young women, many of whom clearly desire to become pregnant. What do you recommend as the best time for the rheumatologist to become involved in communicating with you?

Dr. Edersheim: We communicate throughout the pregnancy, and hopefully before the pregnancy, with the rheumatologist. My idea of the perfect lupus pregnancy would be the one in which I see the patient before she gets pregnant. I see her as she is beginning the whole process, in other words, so that I have a chance to speak with the rheumatologist from the beginning and we can discuss the medications the patient is on and the ideal time for the patient to get pregnant. And we consult with the patient continually during the pregnancy and after because those are all important times for lupus in pregnancy.

Dr. Paget: It must be a complicated issue because on the one hand, the couple desires to have a child. On the other hand, there is a possibility that pregnancy may have a negative effect either on the mother or the child. How do you address the issues of making the appropriate decision?

Dr. Edersheim: Well, we divide the issues into two parts. One is how will the pregnancy affect the fetus, and the other one is how will the fetus affect the mother. So we start by asking if the mother will get worse, will the lupus be deteriorating as a result of the pregnancy. In order to decide that, we have to know from the beginning what condition the mother is in, obviously. With the rheumatologist, we start by knowing the patient's renal function and blood pressure, the medication the patient requires at the time, the history of the disease in the patient, whether the patient's lupus is at a quiet or active time, and whether the patient can be on different medications or no medications.

For the fetus, it is a question of monitoring the fetus throughout the pregnancy. We do this because there are many important things that can impact on the fetus. As long as we keep in mind that there are two patients here and evaluate both patients continually, we usually do fairly well.

Dr. Paget: Are there absolute indications to avoid becoming pregnant when you have lupus? Or is this usually negotiated and discussed with regard to almost a cost/benefit decision?

Dr. Edersheim: That is the issue. There are optimal situations in which you should get pregnant.

Dr. Paget: And what are they?

Dr. Edersheim: The optimal situations occur when the disease is most quiet, particularly if they have renal complications. We would like to see patients get pregnant when their renal manifestations are at the most quiet point and when they require the least amount of medication possible. That doesn't mean that the disease won't get worse during pregnancy. Often just the stress of pregnancy will make the disease worse, but we have the best chance of not having lupus flares during pregnancy if the disease is quiet to start.

In patients who are on the verge of needing dialysis, or patients who are on the verge of being transplanted, those are the times when we would not want the patients to get pregnant. Those are the times when the pregnancy is likely to push them over the edge. Those are the times when the manifestations for the fetus would be worse, particularly prematurity and intrauterine growth restriction.

Dr. Paget: What do you do in a situation if you give a couple a 20% likelihood of a good and safe outcome for the mother and the child and yet they still want to go ahead or they come to you pregnant? What do you bring to bear from an academic medical center to help them get through that?

Dr. Edersheim: You and I have been in that situation together many times. We would focus on taking care of the mother and taking care of the fetus. Pregnancy isn't something that always is planned. When it isn't planned, what we can do is monitor the pregnancy closely by monitoring the mother closely and the fetus closely. How do we do that? With the rheumatologist, we would make sure we evaluate the peripheral manifestations of lupus and the renal disease of the patient. We would make sure that we check for antiphospholipid antibody syndrome, which is a very important part of the effect of lupus on the pregnancy.

In terms of the fetus, in the third trimester, we would use antepartum testing evaluations and ultrasound evaluations to look for fetal growth and placental function. Those are the things that we do in our tertiary care setting. We also have an excellent Neonatal Intensive Care Unit, which is often called upon in these situations.

Dr. Paget: With regard to controlling the disease, are there medications that we as rheumatologists use outside the pregnancy that can actually be continued during pregnancy-- that can be safely taken by the mother?

Dr. Edersheim: Absolutely there are. The one that we use most often is prednisone. Prednisone crosses the placenta in only miniscule amounts, so that it very rarely gets into the fetus in an amount that would be significant. In fact, we often use steroids to help assure the baby's lung development. So this is not a drug that we worry about in pregnancy. With any medication in pregnancy, we deal with what is the condition of the mother, how does the mother's condition impact on the pregnancy, how would medication improve the mother, and is this medication therefore worthwhile.

There are medications that we don't use. For instance, we don't use methotrexate in pregnancy. We don't use cyclophosphamide in pregnancy. But we use the antimalarials, such as hydroxychloroquine, in pregnancy, and there is little if any effect of that medication. So it's a question of whether the mother would significantly deteriorate and whether it would improve the fetal outcome.

Almost any medication can be used if it's a question of life or death in the mother. It's a question of when in the pregnancy, and would the mother be better off delivering the baby or better off continuing the pregnancy with the medication.

Dr. Paget: You mentioned one disorder, antiphospholipid syndrome, that can either be a disorder unto itself or may occur in association with lupus - and about 30% of lupus patients can have it. Those with this syndome have a propensity to clot, and their placentas can be affected by that. What is the optimal way to take care of people with this problem?

Dr. Edersheim: This has been debated for a long time, and originally prednisone was used to treat this problem -- prednisone and aspirin. It has since been found that prednisone and aspirin probably aren't ideal, and that anticlotting medications, particularly aspirin and heparin or aspirin and enoxaparin sodium (Lovenox) are the ideal way of handling it. Again, this is another situation in which vasculature and the placenta are affected.

Dr. Paget: So if somebody has had, for example, prior pregnancy losses, either in early or middle pregnancy, you will then use that information and make a decision to try to make sure that this pregnancy comes to fruition.

Dr. Edersheim: Yes, we use the history as well as laboratory data in evaluating antiphospholipid antibody syndrome. Anyone who has had a loss after ten weeks of pregnancy or in the mid-trimester, even in the third trimester, or anyone who has had a baby who was severely growth-restricted, would be somebody we would consider treating with aspirin and heparin.

Dr. Paget: There is another disorder where the mother has autoantibodies called anti-Ro or anti-La antibodies and their child is subject either to congenital lupus post-partum or even potentially congenital heart block and myocardial disease intrapartum. How do we address that? How do we first find it, and then how do we treat it?

Dr. Edersheim: Congenital heart block is found mostly between 15 and 23 weeks of pregnancy, and the way we find it is by detecting a slowing of heart rate. Neonatal lupus is something that is manifested in the baby after birth. These things are very rare, and they tend to be present with anti-Ro or anti-Ro and anti-La together. Neonatal lupus occurs in about 5% of women and heart block in about roughly the same percentage. Unfortunately, there is no way to prevent these things. Once we see the slowing of heart rate or the development of serositis in the fetus -- we actually see pericardial fluid sometimes -- then we have been treating with high dose prednisone. But there really is no absolute way to treat this in utero.

After the baby is born, pacemakers are implanted, and we often have permanent heart block. In terms of neonatal lupus, this is not the case. Most neonatal lupus reverses in several weeks, and so this is not a permanent condition.

Dr. Paget: And in both of these disorders related to auto-antibodies getting across the placenta and having an effect at a particular time in the heart with regard to the conduction system, and also with regard to skin rash, there may be thrombocytopenia in the congenital lupus that is self-limited. I have always been impressed at the way you take care of patients, your dedication and your advocacy. From what you said before, the communication and collaboration is absolutely key and that includes the patient and the family as well.

Dr. Edersheim: Yes, our patients have to be tremendously dedicated to the pregnancy. It has to be their main goal, because what I ask them to do in pregnancy is so enormous. Very often, I am asking them to stop work completely; very often I am asking them to be in bed. I am asking them to have blood drawn very frequently and to come for antepartum testing. They really need to be dedicated to the pregnancy as their main goal. And the relationships among the obstetrician, the rheumatologist and the patient, with the patient doing the vast majority of the work, is what usually ends in a successful pregnancy or not. If the patient isn't willing to do what needs to be done, all the work in the world by you and me can't make it go.

Dr. Paget: And with regards to becoming pregnant, some people with lupus have difficulty with that. Do they have more difficulty than the general population, and what do you do to try to help them get pregnant?

Dr. Edersheim: The lupus patients who have the most difficulty getting pregnant are those patients who are the most ill. Patients with severe renal dysfunction often have a very difficult time in getting pregnant. Interestingly enough, when they are transplanted, they have a much higher rate of pregnancy., So nature does protect our patients by making it much more difficult for them to get pregnant when they are most sick.

We do treat most of our lupus patients the same way that we treat our non-lupus patients in terms of assistance with reproduction. In other words, we treat them with medications prior to getting pregnant. We also treat them with ovulation induction and in vitro fertilization. The complications of in vitro fertilization in patients who have lupus are higher than those who don't.

Dr. Paget: You are talking about the use of stimulating hormones to have that come about. Is that potentially a trigger to the lupus itself?

Dr. Edersheim: This information is now just being looked at. We used to think that about a third of patients with lupus got worse, and a third stayed the same, and a third got better. Now we know that maybe that happens anyway even if they don't get pregnant. So I don't want to jump the gun here and say that it is much worse in lupus patients. It seems, though, that it may make lupus patients sicker than it does other women.

Dr. Paget: Finally, what about the role of estrogen in women with lupus both with regard to the birth control pill, birth control in general, and also estrogen replacement therapy. Where is our knowledge base at this moment?

Dr. Edersheim: We used to not use birth control pills in patients with lupus, and I think that what we were really seeing is patients with antiphospholipid antibody syndrome who had the higher incidence of clotting. I think now what we need to do is separate the two groups. In other words, we need to make the diagnosis of antiphospholipid antibody syndrome in patients with lupus - or the lack of it. Perhaps those patients who don't have antiphospholipid antibody syndrome are the patients who can be on birth control pills and can be on estrogen replacement, whereas those patients with antiphospholipid antibody syndrome are at higher risk for thrombosis with and without birth control pills, so those would not be a suitable group.

Dr. Paget: There is an NIH study, the SELENA study, that will be finished soon and that will give us better ideas in both of these areas.